Ligand-ricin A chain conjugates (immunotoxins) will be prepared and utilized to modulate the immune response in a highly selective and predictable fashion. Hapten-protein carriers will be used to form immunotoxins and the effect of these immunotoxins on specifically reactive B cells will be studied in adoptive transfer systems and in vivo. The deletion of specific clones by this technique will be evaluated for specificity, duration of unresponsiveness, proof that B cells are the target cells and other parameters. A good deal of attention will be given to developing immunotoxins that are stable in vivo and that have reduced toxicity. Toxicity will be investigated with particular reference to the reticuloendothelial system (RES) with emphasis on the development of immunotoxins that will give minimal and possibly reversible damage to the RES. Immunotoxins will be prepared using major transplantatin antigens and their ability to delete appropriate subsets of specifically reactive T lymphocytes will be investigated in cytotoxic in vitro systems, after intravenous administration with in vitro analysis of lymphoid tissues from such animals and finally, in vivo, with the objective of obliterating specific homograft reactivity. Finally, in the latter phase of this study, regulation of the immune response will be attempted using immunotoxins directed to particular subsets of T lymphocytes that are known to suppress immune responses in specific experimental situations. This information should provide a board base for determining the potential effectiveness of these immunotoxins in clinical medicine.